Knowing the prevalence of potentially avoidable hospitalizations (PAHs) and the factors associated with them is essential if preventive action is to be taken. Studies on PAHs mainly concern adults, and very few have been carried out in South America. To the best of our knowledge, there has been no study on PAHs in French Guiana, particularly among older adults. This case-control study aimed to estimate the prevalence of PAHs in the Guianese population aged over 65 and to analyze their associated factors. We used the 2017-2019 data from the French National Health Service database (Système National des Données de Santé). The patients were age- and sex-matched 1 : 3 with controls without any PAH in 2019. Factors associated with PAHs were investigated through two conditional logistic regression models [one including the Charlson comorbidity index (CCI) and one including each comorbidity of the CCI], with calculation of the adjusted odds ratio (aOR) and 95% confidence interval (CI). The PAH incidence was 17.4 per 1000 inhabitants. PAHs represented 6.6% of all hospitalizations (45.6% related to congestive heart failure or hypertension). A higher CCI was associated with PAHs [aOR 2.2 (95% CI: 1.6, 3.0) and aOR 4.8 (95% CI: 2.4, 9.9) for 1-2 and ≥3 comorbidities, respectively, versus 0], as was immigrant health insurance status [aOR 2.3 (95% CI: 1.3, 4.2)]. Connective tissue disease, chronic pulmonary disease, congestive heart failure, diabetes, and peripheral vascular disease were comorbidities associated with an increased risk of PAHs. While the prevention of PAHs among immigrants is probably beyond the reach of the Guianese authorities, primary care and a public health policy geared toward prevention should be put in place for the French Guianese population suffering from cardiovascular disease in order to reduce PAHs.